This proposal is to study, using mostly the ribosomal RNA synthesis as a model system, the molecular mechanisms of regulation of gene expression in normal and cancer cells. The major objectives of this proposal are: (1) To improve our current understanding of the basic mechanisms of regulation of gene expression by proving (or disproving) that the RNA polymerase system is part of the regulatory machinery and it can take an active part in the expression of genetic information; (2) to probe by dissecting and measuring separately the changes of the RNA polymerase system versus the DNA template availability in response to the various physiological stimuli (such as hormones), as well as pathological agents (such as various chemical carcinogens) that are known to have a profound influence on gene function; (3) by comparative analysis of the similarities and differences in response to the above- mentioned various physiological and pathological agents of the RNA polymerase systems, as well as the DNA template functions, it is hoped to find a clue that may lead to the understanding of the molecular mechanism of neoplasmic transformation.